Cytomegalovirus (CMV) is a member of Betaherpesvirinae in the subfamily Herpesviridae. CMV infects over 70% of the world's adult population and is the most common cause of congenital central nervous system (CNS) infection in humans. Clinically significant CMV disease frequently develops in patients immunocompromised by Human Immunodeficiency Virus (HIV), solid-organ transplantation, and bone-marrow transplantation. Additionally, congenital transmission from a mother with acute infection during pregnancy is a significant cause of neurological abnormalities and deafness in newborns.
Symptomatic disease in immunocompromised individuals can affect almost every organ of the body, resulting in fever of unknown origin, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy. CMV establishes a latent infection in the host and may reactivate during a period of immunosuppression secondary to drugs or intercurrent infection.
In its latent state, the virus is known to reside in stem cells of the myeloid lineage and immune activation and differentiation of these cells can induce viral reactivation and replication. Stem cell populations in other organ systems are also likely to harbor persistent latent infection. Cellular differentiation state is tightly linked to viral expression patterns and this is thought to be due to differentiation-dependent chromatin remodeling of the viral major immediate-early (IE) promoter.
Additionally, association of CMV with several malignancies has been reported, including brain, breast, and colon cancers. A study has confirmed that CMV nucleic acids and proteins are detectable in over 90% of malignant gliomas. Furthermore, a significant proportion of these patients had detectable CMV in the peripheral blood, indicating the presence of an active viral infection.
Current treatment options for eradicating CMV infection includes antiviral agents such as Ganciclovir (a nucleoside analogue that inhibits DNA synthesis), Foscarnet (a DNA chain inhibitor of phosphorylation), Cidofovir (a nucleotide that inhibits DNA replication).
Glioblastoma multiforme (GBM) is a common, highly malignant primary central nervous neoplasm characterized by tumor cell invasion, robust angiogenesis and a mean survival of 15 months. hCMV infection is present in >90% of GBM in humans.
Current treatment options for cancer do not target implicated viruses. There exists a need for methods for such treatment and related compositions.